In anesthetized rats, iontophoretically administered lithium (Li) has an acute, direct depressant effect on spontaneous firing of cerebellar Purkinje neurons, and anatagonizes inhibitory responses of Purkinje to iontophoretic norepinephrine (NE) or to stimulation of the locus coeruleus (LC). Single acute dose of Li (60 mg/kg by gavage) do not alter responses to NE but does show climbing fiber responses. Chronic Li treatment for 10-14 days (by twice daily gavage sufficient to produce blood levels of 0.7-1.0 mEq) reduces Purkinje cell firing and enhances responses to iontophoretic NE. Destruction of NE nerve fibers by 6-OHDA prevents the Li induced reduction in firing rate. Chronic orally administered desmethylimipramine (DMI) also slows Purkinje firing even more than Li; in contrast to Li, DMI significantly increases inhibitory thresholds to iontophoretic NE. Purkinje cell firing returns to normal within 5 days after cessation of either Li or DMI treatment, but enhanced responses to iontophoretically applied NE persist after withdrawal from Li. In collaboration with Professor J. Schultz, University of Tubingen, the same treatment produces changes in norepinephrine activated adenylate cyclase: Li treatment leading to enhanced sensitivity, DMI treatment to reduced sensitivity.